MPDL3280A With Chemoradiation for Lung Cancer

Study Groups and Study Drug Administration:

Each study cycle is 21 days.

If you are found to be eligible to take part in this study, depending on when you join the
study, you will be assigned to 1 of 2 study groups. Up to 10 participants will be assigned to
Group 1 and up to 30 will be assigned to Group 2.

Participants in Groups 1 and 2 will receive standard chemotherapy 1 time each week and
radiation therapy 5 days per week as described below Every cycle you will also receive
MPDL3280A by vein over about 1 hour.

If you are in Group 1, you will receive standard chemotherapy and radiation for 6-7 weeks,
followed by around a 3-8 week "rest period" when you will receive no chemotherapy or
radiation.

If you are in Group 2, you will receive MPDL3280A, standard chemotherapy, and radiation
therapy for 6-7 weeks. This will be followed by a rest period of 3-4 weeks, during which time
you will receive 1 dose of MPDL3280A but no chemotherapy or radiation.

After the rest period, Groups 1 and 2 will both receive MPDL3280A in addition to chemotherapy
for 2 cycles (called the consolidation period). After completing the consolidation period,
you will continue to receive MPDL3280A alone for up to 1 year (called the maintenance
period).

During your first dose of MPDL3280A, your vital signs (blood pressure, pulse, temperature,
and breathing rate) will be measured 60 minutes before the dose, every 15 minutes during the
dose, and 30 minutes after the dose to check for any bad reaction to the study drug. You may
be given standard drugs to help with side effects.

If you need to stop receiving chemotherapy due to side effects, you will also stop receiving
MPDL3280A. If you stop receiving chemotherapy for any other reason, you may continue
receiving MPDL3280A.

Study Visits:

Once a week during Weeks 1-7:

- You will have a physical exam.

- Blood (up to 2 teaspoons) will be drawn for routine tests and to check your liver and
kidney function.

Between Weeks 8-16 you will have a rest period. The rest period could range from 3-8 weeks,
after which time you will return for the consolidation period.

One (1) time during consolidation period, which starts after the rest period, during Weeks
1-3 and Weeks 4-6 of the consolidation period:

- You will have a physical exam.

- Blood (up to 2 teaspoons) will be drawn for routine tests and to check your liver and
kidney function.

- You will have either a CT scan or an FDG-PET/CT scan to check the status of the disease.

After you complete the consolidation period, you will enter the maintenance period. During
every cycle of the maintenance period, blood (about 2 teaspoons) will be drawn for routine
tests.

Every 2 cycles during the maintenance period, for up to 1 year:

- You will have a physical exam.

- You will have either a CT scan or an FDG-PET/CT scan to check the status of the disease.

If the disease appears to come back at any time during the study:

- You will have a physical exam.

- You will have a CT scan or MRI of the brain to check the status of the disease.

- You will have either a CT scan or an FDG-PET/CT of your chest and abdomen to check the
status of the disease.

- You will have a biopsy of any suspicious areas found on the scans to check the status of
the disease.

- Your doctor may choose to continue the study drug and repeat the scans in 6-8 weeks to
check the status of the disease.

- If your doctor feels that the study drug is no longer effective from the information
obtained from the repeat scans, you will be taken off the study drug. You will continue
to be followed up by a schedule determined by your doctor.

- Your doctor may offer alternative treatments if your doctor feels it is in your best
interest.

Length of Treatment:

You may receive the study drug for up to 1 year after starting the consolidation period, as
long as the doctor thinks it is in your best interest. You will no longer be able to receive
study drug if the disease gets worse, if intolerable side effects occur, or if you are unable
to follow study directions.

If you are taken off study during the consolidation or maintenance period due to intolerable
side effects, you will be followed by the study staff as often the doctor thinks is needed
until the side effects get better.

Your active participation on the study will be over after the follow-up visits.

Follow-up Visits:

You will have follow-up visits every 2-4 months for up to 2 years after your last dose of
study drug, unless you leave the study due to side effects or the disease having appeared to
come back. After 2 years, you will have follow-up visits about every 4-6 months based on what
your doctor thinks is best.

At each follow-up visit, the following tests will be performed:

- You will have a physical exam.

- You will have either a CT scan or an FDG-PET/CT scan of your chest and abdomen to check
the status of the disease.

- If your doctor thinks it is needed, blood (up to 2 teaspoons) will be drawn for routine
tests and to check your liver and kidney function.

If you cannot return to MD Anderson for these visits, you may be called by a member of the
study staff every 3-6 months for 4 years after the last dose of study drug. Each call should
last about 10 minutes. The study staff may ask that any tests or scans done by your home
doctor be sent to MD Anderson to check the status of the disease.

Inclusion Criteria:

1. Ability and willingness to provide informed consent

2. Ability and willingness to comply with the requirements of the study protocol

3. Age >/= 18 years.

4. Representative tumor specimens in paraffin blocks (preferred) or at least 10 unstained
slides, with an associated pathology report, requested at any time prior to study
entry. Only tissue from core needle, punch, or excisional biopsy sample collection
will be accepted. Fine-needle aspiration, brushing, and lavage samples are not
acceptable. For all biopsy types, submitted blocks should have sufficient tissue to
generate at least 10 sections, and tissue for which the pathology report specifies
that the overall tumor content is low (e.g., "sparse" or "scant") is not acceptable.

5. Cont'd from #4: If archival tissue is either insufficient or unavailable, the patient
will need to consent to and undergo a pre treatment core or excisional biopsy sample
collection of the tumor. Fine needle aspiration, brushing, and lavage samples are not
acceptable. The immediate unavailability of tissue blocks or unstained slides aside
from the slides needed for diagnostic confirmation of lung cancer does not exclude
patients from this trial. If the patient chooses to not undergo a repeat biopsy aside
from biopsy for diagnostic purposes, the patient will still be eligible to enroll on
2014-0722. However, availability of core or excisional biopsy samples must be
ascertained prior to enrollment.

6. Patients must have histologically confirmed, untreated non-small cell lung cancer that
are considered non-metastatic, unresectable for which chemoradiation is the definitive
therapy.

7. Patients will have the option to enroll on blood collection protocol, LAB09-0983, for
serial collections of blood before, during intervals of treatment, and at follow up
visits. Enrolling on the LAB09-0983 protocol is not required to enroll on the
2014-0722 study.

8. Adequate hematologic and end organ function, defined by the following laboratory
results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
Absolute neutrophil count (ANC) >/= 1500 cells/uL *White Blood Cells (WBC) counts >
2500/uL *Lymphocyte count >/= 500/uL *Platelet count >/= 100,000/uL; for patients with
hematologic malignancies, platelet count >/= 75,000/uL *Hemoglobin >/= 9.0 g/dL *Total
bilirubin with known Gilbert disease who have serum bilirubin level *Aspartate Aminotransferase (AST) and Alanine transaminase (ALT)
9. Cont'd from #8: Serum creatinine /= 50 mL/min
on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age)
x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL)

10. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

11. For female patients of childbearing potential and male patients with partners of
childbearing potential, agreement (by patient and/or partner) to use highly effective
form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year]
when used consistently and correctly) and to continue its use for 12 months after the
last dose of MPDL3280A, and for male patients continued use of contraception must be
for a minimum of 3 months post-treatment.

12. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 as long as
patients are eligible to receive chemotherapy along with concurrent radiotherapy

13. International Normalized (INR) and aPTT who do not receive therapeutic anticoagulation; patients receiving therapeutic
anticoagulation (such as low-molecular weight heparin or warfarin) should be on a
stable dose.

Exclusion Criteria:

1. Patients with any distant metastasis (liver, lung, bone, brain).

2. Any approved anticancer therapy, including chemotherapy, hormonal therapy, or
radiotherapy, within 3 weeks prior to initiation of study treatment; however, the
following are allowed: *Hormone-replacement therapy or oral contraceptives *Herbal
therapy > 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer
therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)

3. Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis, cirrhosis, fatty liver, and inherited liver disease

4. Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia,
chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory
myeloma

5. Pregnancy, lactation, or breastfeeding

6. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

7. Inability to comply with study and follow-up procedures

8. History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
thyroid disease, vasculitis, or glomerulonephritis *Patients with a history of
autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be
eligible. *Patients with controlled Type 1 diabetes mellitus on a stable insulin
regimen may be eligible. *Patients with eczema, psoriasis, lichen simplex chronicus of
vitiligo with dermatologic manifestations only (e.g., patients with psoriatic
arthritis would be excluded) are permitted provided that they meet the following
conditions: *Patients with psoriasis must have a baseline ophthalmologic exam to rule
out ocular manifestations *Rash must cover less than 10% of body surface area (BSA)

9. Cont'd from #9: *Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) *No acute
exacerbations of underlying condition within the last 12 months (not requiring PUVA
[psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents,
oral calcineurin inhibitors, high potency or oral steroids)

10. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan

11. Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications

12. History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic
or acute) or hepatitis C infection *Patients with past or resolved hepatitis B
infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a
positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
*Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for hepatitis C virus ribonucleic acid
(HCV RNA).

13. Active tuberculosis

14. Severe infections within 4 weeks prior to Cycle 1, Day 1 including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia

15. Signs or symptoms of severe infection (sepsis) within 2 weeks prior to treatment
start.

16. Major surgical procedure within 28 days prior to treatment start or anticipation of
need for a major surgical procedure during the course of the study (EBUS and
mediastinoscopy and VATS are not considered major surgical procedures).

17. Administration of a live, attenuated vaccine within 4 weeks before treatment start or
anticipation that such a live attenuated vaccine will be required during the study
*Influenza vaccination should be given during influenza season only (approximately
October to March). Patients must not receive live, attenuated influenza vaccine (e.g.,
FluMist) within 4 weeks prior to treatment start or at any time during the study.

18. Malignancies within 3 years prior to treatment start, with the exception of those with
a negligible risk of metastasis or death and with expected curative outcome (such as
adequately treated carcinoma in situ of the cervix, basal or squamous cell skin
cancer, localized prostate cancer treated surgically with curative intent, or ductal
carcinoma in situ treated surgically with curative intent) or undergoing active
surveillance per standard-of-care management (e.g., CLL Rai Stage 0, prostate cancer
with Gleason score
19. FOLLOWING ARE Medication-Related Exclusion Criteria: *Treatment with systemic
immunostimulatory agents (including but not limited to IFN-a, IL-2) within 6 weeks or
five half-lives of the drug (whichever is shorter) prior to the start of
chemoradiation.Treatment with investigational agent within 4 weeks prior to Cycle 1,
Day 1 (or within five half lives of the investigational product, whichever is longer)

20. Treatment with systemic immunosuppressive medications (including but not limited to
prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1 *Patients who
have received acute, low dose, systemic immunosuppressant medications (e.g., a
one-time dose of dexamethasone for nausea) may be enrolled. *The use of inhaled
corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with
orthostatic hypotension or adrenocortical insufficiency is allowed.

21. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

22. Patients with prior allogeneic bone marrow transplantation or prior solid organ
transplantation